Gender-affirming Hormone Treatment Research Articles

Co-design and usability of an interactive web-based fertility decision aid for transgender youth and young adults.

To develop a patient- and family-centered Aid For Fertility-Related Medical Decisions (AFFRMED) interactive website targeted for transgender and nonbinary (TNB) youth/young adults and their parents to facilitate shared decision-making about fertility preservation interventions through user-centered participatory design. TNB youth/young adults interested in or currently receiving pubertal suppression or gender-affirming hormone treatment and parents of eligible TNB youth/young adults were recruited to participate in a series of iterative human-centered co-design sessions to develop an initial AFFRMED prototype. Subsequently, TNB youth/young adults and parents of TNB youth/young adults were recruited for usability testing interviews, involving measures of usability (i.e., After Scenario Questionnaire, Net Promotor Score, System Usability Scale). Twenty-seven participants completed 18 iterative co-design sessions and provided feedback on 10 versions of AFFRMED (16 TNB youth/young adults and 11 parents). Nine TNB youth/young adults and six parents completed individual usability testing interviews. Overall, participants rated AFFRMED highly on measures of acceptability, appropriateness, usability, and satisfaction. However, scores varied by treatment cohort, with TNB youth interested in or currently receiving pubertal suppression treatment reporting the lowest usability scores. We co-created a youth- and family-centered fertility decision aid prototype that provides education and decision support in an online, interactive format. Future directions include testing the efficacy of the decision aid in improving fertility and fertility preservation knowledge, decisional self-efficacy, and decision satisfaction.

Referrals For Gender-Affirming Hormone Treatment in Croatia's National Network for Transgender Healthcare.

A network of healthcare professionals specializing in transgender care was established in Croatia in 2011, and legal advancements were subsequently made in 2014. Both achievements made gender transition more transparent and thus more attainable in Croatia. This observational study was conducted to assess the number of transgender individuals initiating gender-affirming hormone treatment (GAHT) in Croatia and describes trends in age and sex assigned at birth. Between 2011 and 2022, a total of 111 transgender individuals initiated GAHT. Within the cohort, 52 were assigned male at birth (AMAB) and 59 were assigned female at birth (AFAB). The overall annual incidence rate of transgender individuals initiating GAHT was 0.52 per 100,000 age-adjusted individuals. There was a statistically significant increase (p < 0.01) in transgender individuals commencing GAHT before the COVID-19 pandemic. Furthermore, a rising trend toward masculinizing rather than feminizing treatment was identified (p < 0.05), particularly among younger transgender individuals. The COVID-19 pandemic disrupted these trends in 2020, except for the trend of initiating therapy at a younger age (p < 0.01). The annual incidence and age distribution trends of transgender individuals initiating GAHT in Croatia closely mirrored those in other European countries, with a higher prevalence of individuals assigned female at birth. The study underscores a significant rise in the number of individuals initiating gender-affirming hormone treatment, emphasizing the need for proper legal regulation and healthcare system response.

Body Composition and Metabolic Syndrome Components in Transgender/Gender Diverse Adolescents and Young Adults.

Purpose: The objective of this study was to examine the association of designated sex at birth, body composition, and gender-affirming hormone treatment (GAHT) with the components of metabolic syndrome (MetS) (overweight/obesity, elevated blood pressure [BP], altered glucose metabolism, and dyslipidemia) in transgender/gender diverse (TGD) adolescents and young adults. Methods: TGD individuals underwent body composition studies by bioelectrical impedance analysis according to designated sex at birth, and their muscle-to-fat ratio (MFR) z-scores were calculated. Generalized estimating equations with binary logistic models (n = 326) were used to explore associations while adjusting for potential confounders. Results: A total of 55 TGD females and 111 TGD males, with mean age of 18 ± 1.9 years and median duration of GAHT of 1.4 years (interquartile range = 0.6-2.5), were enrolled. Overall, 118/166 (71%) of the TGD cohort showed evidence of at least one MetS component, with a significantly higher rate among TGD males compared with TGD females (91.1% vs. 50.9%, p < 0.001). TGD males were at increased odds for overweight/obesity, elevated/hypertensive BP, elevated triglycerides (TGs), and an atherogenic dyslipidemia index (TG/high-density lipoprotein cholesterol [HDL-c], TG:HDL-c). The odds of overweight/obesity increased by 44.9 for each standard deviation decrease in the MFR z-score, while the odds for an elevated TG:HDL-c index increased by 3.7. Psychiatric morbidity increased the odds for overweight/obesity by 2.89. Conclusions: After considering confounding variables, the TGD males on GAHT were found to be at an increased risk for cardiometabolic disease. Our observations support the importance of targeted medical nutrition intervention in this group of individuals.

Puberty Blocker, Leuprolide, Reduces Sex Differences in Rough-and-Tumble Play and Anxiety-like Behavior in Juvenile Rats.

We examined the effect of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein messenger RNA levels within the adolescent amygdala, a region important both for rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of gonadotropin-releasing hormone systems may be linked to increased anxiety. These data provide a potential new model to understand the emergence of increased anxiety triggered around puberty. Leuprolide also reduced masculinized levels of rough-and-tumble play behavior, lowered follicle-stimulating hormone, and produced a consistent pattern of reducing or halting sex differences of hormone levels, including testosterone, growth hormone, thyrotropin, and corticosterone levels. Therefore, leuprolide treatment not only pauses sexual development of peripheral tissues, but also reduces sex differences in hormones, brain, and behavior, allowing for better harmonization of these systems following gender-affirming hormone treatment. These data contribute to the intended use of puberty blockers in stopping sex differences from developing further with the potential benefit of lowering anxiety-like behavior.

Adipokine secretion and lipolysis following gender-affirming treatment in transgender individuals.

The organ-specific effects of gender-affirming sex hormone treatment (GAHT) in transgender women (TW) and transgender men (TM) are insufficiently explored. This study investigated the effects of GAHT on adipose tissue function. In a single-center interventional prospective study, 32 adults undergoing GAHT, 15 TW and 17 TM, were examined with anthropometry and abdominal subcutaneous adipose tissue biopsies obtained before initiation of treatment, 1 month after endogenous sex hormone inhibition and three and 11 months after initiated GAHT. Fat cell size, basal/stimulated lipolysis and cytokine secretion in adipose tissue were analyzed. TW displayed an increase in complement component 3a and retinol-binding protein 4 (RBP4) secretion after sex hormone inhibition, which returned to baseline following estradiol treatment. No changes in lipolysis were seen in TW. TM showed downregulation of RBP4 after treatment, but no changes in basal lipolysis. In TM, the estrogen suppression led to higher noradrenaline stimulated (NA) lipolysis that was normalized following testosterone treatment. At 11months, the ratio of NA/basal lipolysis was lower compared to baseline. There were no significant changes in fat cell size in either TW or TM. In TW, gonadal hormone suppression results in transient changes in cytokines and in TM there are some changes in NA-stimulated lipolysis following testosterone treatment. However, despite the known metabolic effects of sex hormones, the overall effects of GAHT on adipose tissue function are small and likely have limited clinical relevance, but larger studies with longer follow-up are needed to confirm these findings. ClinicalTrials.gov Identifier: NCT02518009, Retrospectively registered 7 August 2015.

Reidentification With Birth-Registered Sex in a Western Australian Pediatric Gender Clinic Cohort

Some young people who identify as transgender and seek gender-affirming medical care subsequently reidentify with their sex registered at birth. Evidence regarding the frequency and characteristics of this experience is lacking. To determine the frequency of reidentification and explore associated characteristics in a pediatric gender clinic setting. This retrospective cohort study examined all referrals to the Child and Adolescent Health Service Gender Diversity Service at Perth Children's Hospital between January 1, 2014, and December 31, 2020. The Gender Diversity Service is the sole statewide specialist service in Western Australia that provides children and adolescents up to age 18 years with multidisciplinary assessment, information, support, and gender-affirming medical care. All closed referrals for this study were audited between May 1, 2021, and August 8, 2022. Reidentification with birth-registered sex. The number of referrals closed due to reported reidentification with birth-registered sex was determined, as well as descriptives and frequencies of patient demographics (age, birth-registered sex), informant source, International Statistical Classification of Diseases, Tenth Revision gender-related diagnoses, pubertal status, any gender-affirming medical treatment received, and whether subsequent re-referrals were received. Of 552 closed referrals during the study period, a reason for closure could be determined for 548 patients, including 211 birth-registered males (mean [SD] age, 13.88 [2.00] years) and 337 birth-registered females (mean [SD] age, 15.81 [2.22] years). Patients who reidentified with their birth-registered sex comprised 5.3% (29 of 548; 95% CI, 3.6%-7.5%) of all referral closures. Except for 2 patients, reidentification occurred before or during early stages of assessment (93.1%; 95% CI, 77.2%-99.2%). Two patients who reidentified with their birth-registered sex did so following initiation of puberty suppression or gender-affirming hormone treatment (1.0% of 196 patients who initiated any gender-affirming medical treatment; 95% CI, 0.1%-3.6%). These findings from a pediatric gender clinic audit indicate that a small proportion of patients, and a very small proportion of those who initiated medical gender-affirming treatment, reidentified with their birth-registered sex during the study period. Longitudinal follow-up studies, including qualitative self-report, are required to understand different pathways of gender identity experience.

Effects of gender affirming hormone treatment in transgender individuals - a retrospective cohort study.

Gender affirming hormone treatment (GAHT) results in measurable changes to anthropomorphic, biochemical and hormonal variables that are important to patients and their health care professionals to guide treatment. This study sought to quantify changes which occur in response to initiation of GAHT. We performed a retrospective cohort study of outcomes in transgender and gender diverse (TGD) patients starting GAHT. The primary outcome was proportion of patients and time required to achieve optimal hormone levels after commencement of GAHT. Additional analyses were performed to assess whether clinical and biochemical factors were associated with likelihood of achieving target hormone levels. 345 patients were included. Among 154 transmasculine individuals, 116 (75%) achieved a testosterone level >10 nmol/L during follow-up at a median of 4-months (IQR 4-9). No clinical or biochemical factors were significantly associated with likelihood of reaching therapeutic testosterone concentrations in transmen. Among 191 transfeminine individuals, 131 (72%) achieved a testosterone level <2.0 nmol/L during follow-up at a median of 4-months (IQR 3-9). Factors associated with increased likelihood of testosterone suppression were use of subdermal estradiol implants as well as cyproterone acetate as an androgen antagonist. Changes in differing directions were observed during repeated measures of lipids, liver function, and blood count between transmasculine and transfeminine individuals, reflecting the important effects of testosterone and estradiol on biochemical tests ordered as part of routine clinical care. Most TGD patients achieve target testosterone levels within 9 months of GAHT initiation. Adverse effects of GAHT are rare, and are usually mild.

Nonprescription Hormone Use Among Transgender Women - National HIV Behavioral Surveillance Among Transgender Women, Seven Urban Areas, United States, 2019-2020.

Certain transgender women who seek gender-affirming hormone treatment (GAHT) face economic and social barriers that limit or prevent access to medically supervised GAHT. Transgender women facing such barriers might acquire GAHT without prescription, potentially without proper dosage, administration, and health monitoring in the absence of medical supervision. For this report, survey data were analyzed from 1,165 transgender women in seven urban areas in the United States to examine associations between self-reported use of nonprescription GAHT and known correlates of nonprescription GAHT, including cost, insurance coverage for GAHT, homelessness, receiving money or drugs in exchange for sex during the past 12 months (exchange sex), lack of comfort discussing gender with provider, and lack of health care use. After controlling for complex sampling design, transgender women who reported recent health care use or insurance coverage for GAHT were less likely to report nonprescription GAHT, and those reporting recent exchange sex or recent homelessness were more likely to report nonprescription GAHT. Findings suggest that transgender women were more likely to use GAHT without a prescription in situations of economic and social marginalization (e.g., disengagement from health care, lack of insurance or trans-specific health care, homelessness, or engagement in sex work). Public health professionals can use these results to design effective interventions to facilitate prescribed hormone use among transgender women in the United States, although access to housing, trans-affirming health care, and insurance coverage might be needed to prevent nonprescription use.

CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment

Gender identity refers to the consciousness of being a man, a woman or other condition. Although it is generally congruent with the sex assigned at birth, for some people it is not. If the incongruity is distressing, it is defined as gender dysphoria (GD). Here, we measured whole-genome DNA methylation by the Illumina © Infinium Human Methylation 850k array and reported its correlation with cortical thickness (CTh) in 22 transgender men (TM) experiencing GD versus 25 cisgender men (CM) and 28 cisgender women (CW). With respect to the methylation analysis, TM vs. CW showed significant differences in 35 CpGs, while 2155 CpGs were found when TM vs. CM were compared. With respect to correlation analysis, TM showed differences in methylation of CBLL1 and DLG1 genes that correlated with global and left hemisphere CTh. Both genes were hypomethylated in TM compared to the cisgender groups. Early onset TM showed a positive correlation between CBLL1 and several cortical regions in the frontal (left caudal middle frontal), temporal (right inferior temporal, left fusiform) and parietal cortices (left supramarginal and right paracentral). This is the first study relating CBLL1 methylation with CTh in transgender persons and supports a neurodevelopmental hypothesis of gender identity.

Venous Thrombo-Embolism Is Rare in Transgender and Gender Non-Binary Adolescents and Youth: A Multicenter Observational Study

Introduction An increasing number of adolescents and youth identify as transgender or gender non-binary (TNB). Gender-affirming hormone treatment (GAHT), including estrogen or testosterone therapy increase appearance congruence and psychological functioning, and decrease depression, anxiety and suicidal ideation. In adult TNB patients, estrogen therapy is associated with an increased risk of venous thromboembolism (VTE), while the thromboembolic risk of testosterone is less clear. A recent cross-sectional study conducted at Boston Children's Hospital (BCH) suggested that VTE is rare in TNB adolescents and youth and typically occurs in the setting of additional risk factors. Additionally, GAHT was not identified as a significant risk factor for thrombosis in this cohort. Herein, we sought to confirm our preliminary findings across 49 free-standing children's hospitals using an administrative database. Methods The study was deemed exempt by the Institutional Review Board at BCH. Administrative approval was obtained through the Children's Hospital Association. Data for this study were obtained from Pediatric Health Information System (PHIS), an administrative database that contains clinical and resource utilization data from inpatient, ambulatory surgery, emergency department, and observation encounters across 49 tertiary-care children's hospitals in the United States. Data quality and reliability are assured through a joint effort between CHA and participating institutions. International Classification of Disease, 9 th and 10 th Editions (ICD9/ICD10) codes were used to identify eligible subjects, defined as children (from birth to 21 years of age) hospitalized with VTE between 1/1/2012-12/31/2021 at one of 49-participating hospitals. ICD9/ICD10 codes for gender dysphoria were used to identify TNB adolescents and youth. Mean (SD) or median (range) were calculated for continuous data, and frequency with 95% confidence interval for categorical data. Results During the study period, 39,503 unique patients (birth-assigned females: 18,395 [47%]) were diagnosed with VTE. Mean age (SD) at VTE diagnosis was 7.7 (7.3) years. Only 23 (0.06%) patients had an ICD9/ICD10 diagnosis code for gender dysphoria. Of these 23 patients, six (26%) were birth-assigned males and 17 (74%) were birth-assigned females. Among these 23 patients, the median (range) age at VTE diagnosis was 16.2 (11.6, 20.5) years. VTE location for patients identified as TNB included: lower extremities (n=8), upper extremities (n=5), pulmonary embolism (n=5), cerebral sinus venous thrombosis (CSVT) (n=1), and other (n=4). Demographic data for the overall cohort and the subset of TNB patients are summarized in Table 1. 2,790 patients with a VTE diagnosis died prior to hospital discharge, while none of the 23 VTE patients identified as TNB died prior to hospital discharge. Only 2/23 (8.7%) TNB patients with VTE had a diagnosis code for hormone replacement therapy (HRT). One patient was a birth-assigned male, and one was a birth-assigned female. Among the 23 TNB patients with VTE, none had congenital heart disease, ten (43%) were obese, three (13%) had chronic renal disease, two (9%) had cancer and one (4%) had inflammatory bowel disease (Table 1). Discussion These data support our initial observation that VTE is extremely rare in TNB adolescents and youth and typically occurs in the setting of additional risk factors for VTE including cancer, renal disease, obesity, and inflammatory bowel disease. Only 2/23 TNB patients had a simultaneous code for HRT, suggesting that HRT may not be a significant risk factor for VTE in this cohort. A limitation of this investigation is the inability to estimate how many TNB patients received care at the participating centers during the study period.

Gender-affirming hormone therapy effect on cortisol levels in trans males and trans females.

Previous studies have shown differences in baseline and stimulated cortisol levels between men and women. Whether this difference is secondary to sex hormones or to other factors, such as genetic or epigenetic changes, is unknown. We investigated the effect of gender-affirming hormone treatment (GAHT) on the hypothalamo-pituitary-adrenal axisof transgender subjects in an effort to throw light on this question. Ten transgender males (TM) and eighttransgender females (TF) underwent a low-dose (1 µg) adrenocorticotropic hormone (ACTH) stimulation test before and 6 months after GAHT initiation. Serum total, free and salivary cortisol (SC) levels were measured at baseline and at 20, 30and 40 min. For the TM, all three levels were significantly lower at several time points after ACTH injection compared to pretreatment levels following 6 months of treatment (p < .05). Likewise, the overall SCresponse as calculated by the area under the curve was significantly lower (p = .0053). For the TF, the basal total cortisol (TC) level increased after 6 months of treatment (p < .01) while ACTH-stimulated SClevels decreased significantly. The basal ACTH levels were significantly lower following hormonal therapy (p < .001). Stimulated salivary cortisol levels decreased significantly after 6 months of GAHT in both male and female transgender subjects, possibly reflecting a decreased state of anxiety associated with treatment initiation. Additionally, basal and stimulated serum TC levels increased after hormonal treatment in the TF, probably secondary to the effect of oestrogen on cortisol-binding globulin.

Gender-affirming hormone treatment: friend or foe? Long-term follow-up of 755 transgender people.

Gender-affirming hormone treatment (GAHT) is one of the main demands of transgender and gender diverse (TGD) people, who are usually categorised as transgender assigned-male-at birth (AMAB) and assigned-female-at birth (AFAB). The aim of the study is to investigate the long-term therapeutic management of GAHT, considering hormonal targets, treatment adjustments and GAHT safety. A retrospective, longitudinal, observational, multicentre clinical study was carried out. Transgender people, both AMAB and AFAB, were recruited from two Endocrinology Units in Italy (Turin and Modena) between 2005 and 2022. Each subject was managed with specific and personalized follow-up depending on the clinical practice of the Centre. All clinical data routinely collected were extracted, including anthropometric and biochemical parameters, lifestyle habits, GAHT regime, and cardiovascular events. Three-hundred and two transgender AFAB and 453 transgender AMAB were included. Similar follow-up duration (p = 0.974) and visits' number (p = 0.384) were detected between groups. The transgender AFAB group reached therapeutic goals in less time (p = 0.002), fewer visits (p = 0.006) and fewer adjustments of GAHT scheme (p = 0.024). Accordingly, transgender AFAB showed a higher adherence to medical prescriptions compared to transgender AMAB people (p < 0.001). No significantly increased rate of cardiovascular events was detected in both groups. Our real-world clinical study shows that transgender AFAB achieve hormone target earlier and more frequently in comparison to transgender AMAB individuals. Therefore, transgender AMAB people may require more frequent check-ups in order to tailor feminizing GAHT and increase therapeutic adherence.

SAT402 A Multimodal Curriculum To Improve Medical Student Gender-affirming Communication Skills

Abstract Disclosure: R.B. Jones: None. C. Maskart: None. J.M. Radway: None. A. Amaro: None. S. Cardillo: None. Introduction: Transgender and gender-diverse (TGD) people, whose gender identities and/or expression(s) exist outside the gender binary, are marginalized in healthcare. They often meet medical providers who do not have the skills or experience to address issues relevant to TGD persons. This can lead to suboptimal care and in some situations, micro- or macroaggressions. Physicians can help create a welcoming environment for gender-diverse people by addressing them in a respectful and affirming way. Physicians and trainees, however, rarely receive formal instruction or simulated training to practice providing gender-affirming care. Objective: The goal of the session was to give medical students an opportunity to observe, practice, and debrief medical encounters with gender-diverse patients. We collaborated with TGD standardized patients (SPs) and the standardized patient program to design a multimodal communication skills session: - 20-minute didactic lecture reviewing health care disparities affecting gender-diverse individuals and examples of gender-affirming language - 15-minute video encounter showing a provider misgendering a TGD SP then recovering, followed by a provider not misgendering the patient - 45-minute small group session where students take a history for a patient beginning hormone treatment to facilitate gender transition. Students receive feedback from the SP and preceptor. Notable design characteristics include TGD SPs involved in the curriculum and case scenario creation, piloting of the session, and recruitment of only faculty preceptors with clinical experience in gender-affirming hormone treatment (GAHT) to facilitate sessions. Results/Conclusions: 124 students completed the curriculum. Prior to and one week after the curriculum, students completed a 5-point self-assessment survey measuring six items: pronoun use, recovery from misgendering, communication skills with TGD knowledge, ability to take a targeted history, mental health effects of GAHT, and how to assess for treatment goals, skills, and attitudes with respect to gender-diverse healthcare. 85 students completed the pre-survey and 32 students completed the post-survey. When results were dichotomized to low (1-3 on scale) and high (4-5) comfort or ability, over 50% of students who completed the post-survey changed from low to high in their self-rated ability to take a targeted history, knowledge of the mental health effects of GAHT and how to assess for treatment goals. Qualitatively, SPs thought preceptors were particularly knowledgeable and affirming in the topic. Student feedback suggested the need for smaller group sizes which will be adapted for future iterations. Presentation: Saturday, June 17, 2023

The Ethical Mandate of Fertility Preservation Coverage for Transgender and Gender Diverse Individuals

For individuals pursuing medically assisted gender transition, gender-affirming surgical treatments, such as oophorectomy (removal of the ovaries) and orchiectomy (removal of the testicles), cause sterility, and gender-affirming hormone treatment with medications (i.e., testosterone and estrogen) may negatively impact infertility. The major United States (US) medical associations already endorse fertility preservation (FP) through cryopreservation (i.e., “freezing” egg and sperm) for transgender individuals. Despite these endorsements from the relevant medical societies, medical insurance coverage for FP remains very limited in the US. Given the high out-of-pocket costs for FP services, fertility preservation remains financially out of reach for many transgender individuals who may desire it. We present an ethical justification for universal FP coverage for all transgender and gender diverse (TGD) individuals who request this option during medically assisted gender transition. First, we argue that gender-affirming medical care is analogous to other medical interventions and treatment regimens that compromise fertility, such as cancer care, and that both types of interventions need to be afforded the same medical benefits and assistance in pursuing fertility goals. Second, we argue that the lack of FP for transgender individuals contributes to the ongoing and profound transphobia and anti-trans bias that has been exacerbated in the past several years across the healthcare landscape in the United States. We argue that the provision of FP coverage for transgender individuals is necessary for clinicians and third-party payers to state their unequivocal support for TGD patients and their healthcare needs.

The dose-dependent effect of estrogen on bone mineral density in trans girls.

Treatment in transgender girls can consist of puberty suppression (PS) with a gonadotropin-releasing hormone agonist (GnRHa) followed by gender-affirming hormonal treatment (GAHT) with estrogen. Bone mineral density (BMD) Z-scores decrease during PS and remain relatively low during GAHT, possibly due to insufficient estradiol dosage. Some adolescents receive high-dose estradiol or ethinyl estradiol (EE) to limit growth allowing comparison of BMD outcomes with different dosages. Retrospective study. Adolescents treated with GnRHa for ≥1 year prior to GAHT followed by treatment with a regular estradiol dose (gradually increased to 2 mg), 6 mg estradiol or 100-200 µg EE were included to evaluate height-adjusted BMD Z-scores (HAZ scores) on DXA. Eighty-seven adolescents were included. During 2.3 ± 0.7 years PS, lumbar spine HAZ scores decreased by 0.69 [95% confidence interval (CI) -0.82 to -0.56)]. During 2 years HT, lumbar spine HAZ scores hardly increased in the regular group (0.14, 95% CI -0.01 to 0.28, n = 59) vs 0.42 (95% CI 0.13 to 0.72) in the 6 mg group (n = 13), and 0.68 (95% CI 0.20 to 1.15) in the EE group (n = 15). Compared with the regular group, the increase with EE treatment was higher (0.54, 95% CI 0.05 to 1.04). After 2 years HT, HAZ scores approached baseline levels at start of PS in individuals treated with 6 mg or EE (difference in 6 mg group -0.20, 95% CI -0.50 to 0.09; in EE 0.17, 95% CI -0.16 to 0.50) but not in the regular group (-0.64, 95% CI -0.79 to -0.49). Higher estrogen dosage is associated with a greater increase in lumbar spine BMD Z-scores. Increasing dosage up to 2 mg estradiol is insufficient to optimize BMD and approximately 4 mg may be required for adequate serum concentrations.

Impaired in vitro fertilization outcomes following testosterone treatment improve with washout in a mouse model of gender-affirming hormone treatment

The impact of gender-affirming testosterone on fertility is poorly understood, with ovarian histopathologic studies showing variable results, some with a detrimental effect on reproductive capacity and uncertain reversibility. Assisted reproductive outcome data are restricted to small case series that lack the ability to inform clinical practice guidelines and limit fertility preservation counseling for transgender and nonbinary individuals. This study aimed to determine the impact of current testosterone and testosterone washout on invitro fertilization outcomes in a mouse model for gender-affirming hormone treatment. We hypothesized that current or previous testosterone treatment would not affect invitro fertilization outcomes. C57BL/6N female mice (n=120) were assigned to 4 treatment groups: (1) current control, (2) current testosterone, (3) control washout, and (4) testosterone washout. Testosterone implants remained in situ for 6 or 12 weeks, representing the short- and long-term treatment arms, respectively. Current treatment groups underwent ovarian stimulation with implants in place, and washout treatment groups were explanted and had ovarian stimulation after 2 weeks. Oocytes were collected, fertilized, and cultured invitro, with one arm continuing to the blastocyst stage and the other having transfer of cleavage-stage embryos. Statistical analysis was performed using GraphPad Prism, version 9.0 and R statistical software, version 4.1.2, with statistical significance defined by P<.05. Current long-term testosterone treatment impaired invitro fertilization outcomes, with fewer mature oocytes retrieved (13.7±5.1 [standard deviation] vs 28.6±7.8 [standard deviation]; P<.0001) leading to fewer cleavage-stage embryos (12.1±5.1 vs 26.5±8.2; P<.0001) and blastocysts (10.0±3.2 vs 25.0±6.5; P<.0001). There was recovery of invitro fertilization outcomes following washout in the short-term treatment cohort, with incomplete reversibility in the long-term cohort. Testosterone did not negatively affect maturity, fertilization, or blastulation rates. In a mouse model of gender-affirming hormone treatment, testosterone negatively affected oocyte yield without affecting oocyte quality. Our findings suggest that testosterone reversibility is duration-dependent. These results demonstrate the feasibility of invitro fertilization without testosterone discontinuation while supporting a washout period for optimization of mature oocyte yield.

P-409 Oocyte cryopreservation following ovarian stimulation for fertility preservation in transgender men: a French case series

Abstract Study question To evaluate the feasibility and results of a fertility preservation program for transgender men. Summary answer Ovarian stimulation outcomes are similar between transgender men and oocyte donation candidates, leading to a satisfactory mean number of cryopreserved oocytes. What is known already The reproductive potential of transgender people may be impaired by gender-affirming hormone treatment (GAHT) and is obviously suppressed in case of gender-affirming surgery involving bilateral ovariectomy and/or hysterectomy. The evolution of medical support for transgender people has made fertility preservation strategies possible. Fertility preservation in transgender men mainly relies on oocyte cryopreservation following controlled ovarian stimulation. However, few data are available to date on the subject, concerning small sample sizes, so no reliable conclusions can be drawn about the feasibility and efficiency of fertility preservation procedures in trans men. Study design, size, duration This retrospective study reports the results of fertility preservation counselling in 118 transgender men referred to our fertility centre from September 2018 to December 2022. Among them, 16 benefited from oocyte cryopreservation. Ovarian stimulation outcomes were compared with those of cisgender oocyte donors. Participants/materials, setting, methods Sixteen transgender men benefited from oocyte cryopreservation following ovarian stimulation and were matched 1:1 to cisgender oocyte donors according to age and body mass index. Antral follicle count and serum AMH levels were systematically measured. Primary outcomes included duration of the stimulation, total FSH dose, peak serum estradiol, oocyte yield, number of mature oocytes, and maturity rate (mature oocytes/total oocytes collected). Results were compared using Fisher’s exact or Wilcoxon’s rank sum tests. Main results and the role of chance One hundred and eighteen transgender men were referred in our centre for fertility preservation counselling. Among them, 95 asked for a medical consultation, and 86 came to the appointment. Following the consultation, only 16 (18.6%) finally decided to benefit from oocyte cryopreservation following ovarian stimulation, including 2 that had already started testosterone therapy. Sixteen presumably fertile oocyte donors were matched based on age and BMI. Mean age of trans’ men was 23.9 ± 5.0. Basal ovarian reserve tests showed satisfactory results in trans’ men and oocyte donors, with similar AMH (4.5 ± 2.3 vs. 4.4 ± 3.2, respectively, NS) but lower AFC in trans’men than in oocyte donors (13.8 ± 11.0 vs. 26.7 ± 10.1, p = 0.033). This result may be explained by a more frequent use of the abdominal approach to assess AFC in the transgender group. Ovarian stimulation outcomes were comparable, with no differences in the duration of stimulation, total FSH dose and peak estradiol levels, leading to a comparable mean number of mature oocyte (15.4 ± 9.9 vs. 17.2 ± 10.6, respectively, NS). Thirteen out 16 transgender men had 10 or more cryopreserved mature oocyte following a single procedure. Limitations, reasons for caution Only a low percentage of trans men that were referred to our centre finally chose to perform oocyte cryopreservation, leading to a small sample size. The majority of them had not started any GAHT, preventing us to evaluate the potential consequences of these treatments on ovarian stimulation outcomes. Wider implications of the findings While parenthood strategies for transgender people have long been ignored, fertility preservation is an important issue to consider, especially because medical treatments and surgeries may be undertaken in very young adults. Oocyte cryopreservation seems to represent a feasible way for trans men to preserve their fertility for future biological parenting. Trial registration number N/A

Safety of gender affirming treatment in assigned female at birth transgender people and association of androgen and estrogen β receptor polymorphisms with clinical outcomes.

Gender affirming hormone treatment (GAHT) with androgens in assigned female at birth (AFAB) people with Gender Incongruence (GI) can induce and maintain variable phenotypical changes, but individual response may be genetically determined. To clarify the role of AR and ERβ polymorphisms we prospectively evaluated AFAB subjects undergoing virilizing GAHT. Fifty-two AFAB people with confirmed GI were evaluated before (T0) and after 6 (T6) and 12 months (T12) of testosterone enanthate 250 mg i.m. every 28 days. Hormone profile (testosterone, estradiol), biochemical (blood count, glyco-metabolic profile) and clinical parameters (Ferriman-Gallwey score, pelvic organs) were evaluated at each time-point, as well as number of CAG and CA repeats for AR and ERβ, respectively. All subjects have successfully achieved testosterone levels within normal male ranges and improved their degree of virilization, in absence of significant side effects. Hemoglobin, hematocrit and red blood cells were significantly increased after treatment, but within normal ranges. Ultrasound monitoring of pelvic organs showed their significant reduction already after 6 months of GATH, in absence of remarkable abnormalities. Furthermore, a lower number of CAG repeats was associated with a higher Ferriman-Gallwey score post treatment and a higher number of CA repeats was associated with uterine volume reduction. We confirmed safety and efficacy of testosterone treatment on all measured parameters. This preliminary data hints a future role of genetic polymorphisms to tailor GAHT in GI people, but evaluation on a larger cohort is necessary as the reduced sample size could limit data generalization at this stage.

Skin cancer incidence in transgender individuals receiving gender-affirming hormone treatment: a nationwide cohort study in the Netherlands.

Development of skin cancer, in particular melanoma, has been linked to sex hormones. We aimed to determine the incidence of skin cancer in transgender individuals receiving gender-affirming hormone treatment (GAHT). In this nationwide retrospective cohort study, clinical information of participants who visited our clinic between (the years) 1972 and 2018 and received GAHT was integrated with national pathology and cancer statistics data in order to assess skin cancer incidence. Standardized incidence ratios (SIRs) were calculated. The cohort consisted of 2,436 trans women and 1,444 trans men. The median age at the start of GAHT was 31 years (IQR 24-42) in trans women and 24 years (IQR 20-32) in trans men. The median follow-up time for trans women was 8 years (IQR 3-18) with a total follow-up time of 29,152 years and 4 years (IQR 2-12) with a total follow-up time of 12,469 years for trans men. Eight trans women were diagnosed with melanoma (SIR 1.80 [95% CI 0.83-3.41] vs. all men; SIR 1.40 [0.65-2.65] vs. all women), and seven developed squamous cell carcinoma (SIR 0.78 [0.34-1.55] vs. all men; SIR 1.15 [0.50-2.27] vs. all women). Two trans men developed melanoma (SIR 1.05 [0.18-3.47] vs. all men; SIR 0.77 [0.14-2.70] vs. all women). GAHT did not appear to affect skin cancer incidence in this large cohort of transgender individuals. As skin cancer incidence increases with age and the proportion of elderly subjects is currently limited in this cohort, it will be worthwhile to repeat this analysis in the future.

Gender Affirming Hormonal Treatment (GAHT) and Demographics of Slovenian Transgender Adults

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)